CA1339304C - Liaison de ligands sur une cible commune - Google Patents
Liaison de ligands sur une cible communeInfo
- Publication number
- CA1339304C CA1339304C CA000586425A CA586425A CA1339304C CA 1339304 C CA1339304 C CA 1339304C CA 000586425 A CA000586425 A CA 000586425A CA 586425 A CA586425 A CA 586425A CA 1339304 C CA1339304 C CA 1339304C
- Authority
- CA
- Canada
- Prior art keywords
- probe
- polynucleotide
- target
- reaction product
- coumarin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000000523 sample Substances 0.000 claims abstract description 466
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 109
- 239000003446 ligand Substances 0.000 claims abstract description 87
- 125000000524 functional group Chemical group 0.000 claims abstract description 76
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 73
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 73
- 239000002157 polynucleotide Substances 0.000 claims abstract description 73
- 238000000034 method Methods 0.000 claims abstract description 65
- 230000004913 activation Effects 0.000 claims abstract description 16
- 230000027455 binding Effects 0.000 claims description 55
- 238000009739 binding Methods 0.000 claims description 55
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 49
- 239000002253 acid Substances 0.000 claims description 41
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 claims description 34
- -1 psoralens Chemical class 0.000 claims description 32
- 235000001671 coumarin Nutrition 0.000 claims description 28
- 238000001514 detection method Methods 0.000 claims description 25
- 229960000956 coumarin Drugs 0.000 claims description 22
- 150000004775 coumarins Chemical class 0.000 claims description 20
- 239000003153 chemical reaction reagent Substances 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 230000003213 activating effect Effects 0.000 claims description 8
- 150000002576 ketones Chemical class 0.000 claims description 8
- CFNMUZCFSDMZPQ-GHXNOFRVSA-N 7-[(z)-3-methyl-4-(4-methyl-5-oxo-2h-furan-2-yl)but-2-enoxy]chromen-2-one Chemical compound C=1C=C2C=CC(=O)OC2=CC=1OC/C=C(/C)CC1OC(=O)C(C)=C1 CFNMUZCFSDMZPQ-GHXNOFRVSA-N 0.000 claims description 7
- 230000005284 excitation Effects 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 150000001336 alkenes Chemical class 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- 230000008033 biological extinction Effects 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 229920000098 polyolefin Polymers 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 150000001540 azides Chemical class 0.000 claims description 3
- 150000001746 carotenes Chemical class 0.000 claims description 3
- 235000005473 carotenes Nutrition 0.000 claims description 3
- 150000001454 anthracenes Chemical class 0.000 claims description 2
- 150000004777 chromones Chemical class 0.000 claims description 2
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims description 2
- 150000003220 pyrenes Chemical class 0.000 claims description 2
- 150000004053 quinones Chemical class 0.000 claims description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 claims 2
- RFBSUCSDHSKDGN-UHFFFAOYSA-N 2-(6-methoxy-2-oxochromen-7-yl)oxybutanoic acid Chemical compound O1C(=O)C=CC2=C1C=C(OC(CC)C(O)=O)C(OC)=C2 RFBSUCSDHSKDGN-UHFFFAOYSA-N 0.000 claims 1
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 claims 1
- 101100111947 Arabidopsis thaliana CYP72C1 gene Proteins 0.000 claims 1
- 101100439244 Glycine max CHI2-A gene Proteins 0.000 claims 1
- AOJDZKCUAATBGE-UHFFFAOYSA-N bromomethane Chemical compound Br[CH2] AOJDZKCUAATBGE-UHFFFAOYSA-N 0.000 claims 1
- 101150071577 chi2 gene Proteins 0.000 claims 1
- HFPGRVHMFSJMOL-UHFFFAOYSA-N dibromomethane Chemical compound Br[CH]Br HFPGRVHMFSJMOL-UHFFFAOYSA-N 0.000 claims 1
- ZJULYDCRWUEPTK-UHFFFAOYSA-N dichloromethyl Chemical compound Cl[CH]Cl ZJULYDCRWUEPTK-UHFFFAOYSA-N 0.000 claims 1
- 238000012544 monitoring process Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 29
- 108020004414 DNA Proteins 0.000 description 74
- 102000053602 DNA Human genes 0.000 description 74
- 238000006243 chemical reaction Methods 0.000 description 42
- 239000000243 solution Substances 0.000 description 35
- 229920002477 rna polymer Polymers 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 230000005291 magnetic effect Effects 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- 239000000499 gel Substances 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 238000003556 assay Methods 0.000 description 16
- 239000011324 bead Substances 0.000 description 16
- 238000009396 hybridization Methods 0.000 description 16
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 16
- 150000007523 nucleic acids Chemical class 0.000 description 16
- 229910001868 water Inorganic materials 0.000 description 16
- CDHSCTCRBLLCBJ-UHFFFAOYSA-N 5-hydroxy-2H-chromen-2-one Chemical compound O1C(=O)C=CC2=C1C=CC=C2O CDHSCTCRBLLCBJ-UHFFFAOYSA-N 0.000 description 14
- 125000004429 atom Chemical group 0.000 description 14
- 230000001413 cellular effect Effects 0.000 description 14
- 102000039446 nucleic acids Human genes 0.000 description 14
- 108020004707 nucleic acids Proteins 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 239000000020 Nitrocellulose Substances 0.000 description 13
- FJWGYAHXMCUOOM-QHOUIDNNSA-N [(2s,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6s)-4,5-dinitrooxy-2-(nitrooxymethyl)-6-[(2r,3r,4s,5r,6s)-4,5,6-trinitrooxy-2-(nitrooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-3,5-dinitrooxy-6-(nitrooxymethyl)oxan-4-yl] nitrate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O)O[C@H]1[C@@H]([C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@@H](CO[N+]([O-])=O)O1)O[N+]([O-])=O)CO[N+](=O)[O-])[C@@H]1[C@@H](CO[N+]([O-])=O)O[C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O FJWGYAHXMCUOOM-QHOUIDNNSA-N 0.000 description 13
- 238000001994 activation Methods 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 229940079938 nitrocellulose Drugs 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 230000003321 amplification Effects 0.000 description 12
- 239000002609 medium Substances 0.000 description 12
- 238000003199 nucleic acid amplification method Methods 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000007792 addition Methods 0.000 description 11
- 229920001220 nitrocellulos Polymers 0.000 description 11
- 239000002245 particle Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 230000000295 complement effect Effects 0.000 description 9
- 230000002255 enzymatic effect Effects 0.000 description 9
- 238000012545 processing Methods 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 8
- FYIDLHBPNPJPRD-UHFFFAOYSA-N 2-(7-methoxy-2-oxochromen-6-yl)oxybutanoic acid Chemical compound C1=CC(=O)OC2=C1C=C(OC(CC)C(O)=O)C(OC)=C2 FYIDLHBPNPJPRD-UHFFFAOYSA-N 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- 229960001701 chloroform Drugs 0.000 description 7
- 238000004132 cross linking Methods 0.000 description 7
- 238000006911 enzymatic reaction Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 230000002285 radioactive effect Effects 0.000 description 7
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 6
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000001931 aliphatic group Chemical group 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- SYTYLPHCLSSCOJ-UHFFFAOYSA-N isoscopoletin Chemical compound O1C(=O)C=CC2=C1C=C(OC)C(O)=C2 SYTYLPHCLSSCOJ-UHFFFAOYSA-N 0.000 description 6
- RQSKEMWBCJHQMX-UHFFFAOYSA-N isoscopoletin Natural products COc1cc2OC(=O)CCc2cc1O RQSKEMWBCJHQMX-UHFFFAOYSA-N 0.000 description 6
- 238000007899 nucleic acid hybridization Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 6
- HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical compound C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 description 5
- ZOJAINJCZSVZGW-UHFFFAOYSA-N 6-aminochromen-2-one Chemical compound O1C(=O)C=CC2=CC(N)=CC=C21 ZOJAINJCZSVZGW-UHFFFAOYSA-N 0.000 description 5
- 108020003215 DNA Probes Proteins 0.000 description 5
- 239000003298 DNA probe Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 150000002540 isothiocyanates Chemical class 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- RMERXEXZXIVNBF-UHFFFAOYSA-N 6-nitrochromen-2-one Chemical compound O1C(=O)C=CC2=CC([N+](=O)[O-])=CC=C21 RMERXEXZXIVNBF-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 4
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- UIZLQMLDSWKZGC-UHFFFAOYSA-N cadmium helium Chemical compound [He].[Cd] UIZLQMLDSWKZGC-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000001351 cycling effect Effects 0.000 description 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- 238000004925 denaturation Methods 0.000 description 4
- 230000036425 denaturation Effects 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 229920001519 homopolymer Polymers 0.000 description 4
- HQCYVSPJIOJEGA-UHFFFAOYSA-N methoxycoumarin Chemical compound C1=CC=C2OC(=O)C(OC)=CC2=C1 HQCYVSPJIOJEGA-UHFFFAOYSA-N 0.000 description 4
- 230000002186 photoactivation Effects 0.000 description 4
- 229920002401 polyacrylamide Polymers 0.000 description 4
- 238000004153 renaturation Methods 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- RODXRVNMMDRFIK-UHFFFAOYSA-N scopoletin Chemical compound C1=CC(=O)OC2=C1C=C(OC)C(O)=C2 RODXRVNMMDRFIK-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
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- VKIGAWAEXPTIOL-UHFFFAOYSA-N 2-hydroxyhexanenitrile Chemical compound CCCCC(O)C#N VKIGAWAEXPTIOL-UHFFFAOYSA-N 0.000 description 3
- 229930024421 Adenine Natural products 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- UFMWIMXDXFIBJF-GXSJLCMTSA-N [[(2s,5r)-5-[4-(3-aminopropylamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1N=C(NCCCN)C=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)CC1 UFMWIMXDXFIBJF-GXSJLCMTSA-N 0.000 description 3
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- OMFRMAHOUUJSGP-IRHGGOMRSA-N bifenthrin Chemical compound C1=CC=C(C=2C=CC=CC=2)C(C)=C1COC(=O)[C@@H]1[C@H](\C=C(/Cl)C(F)(F)F)C1(C)C OMFRMAHOUUJSGP-IRHGGOMRSA-N 0.000 description 3
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 3
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- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
- FSYZMWXBIPICHO-UHFFFAOYSA-N ethyl 2-(2-oxochromen-7-yl)oxybutanoate Chemical compound C1=CC(=O)OC2=CC(OC(CC)C(=O)OCC)=CC=C21 FSYZMWXBIPICHO-UHFFFAOYSA-N 0.000 description 3
- XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 3
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- 238000005755 formation reaction Methods 0.000 description 3
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- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 230000002934 lysing effect Effects 0.000 description 3
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 3
- 239000006249 magnetic particle Substances 0.000 description 3
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 3
- 229910052753 mercury Inorganic materials 0.000 description 3
- PQLQSEUZCLHNEE-UHFFFAOYSA-N methyl 3-(2,6-dimethoxyphenyl)prop-2-enoate Chemical compound COC(=O)C=CC1=C(OC)C=CC=C1OC PQLQSEUZCLHNEE-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 150000008300 phosphoramidites Chemical class 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000010926 purge Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/14—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 6 and unsubstituted in position 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/18—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted otherwise than in position 3 or 7
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Control Of Driving Devices And Active Controlling Of Vehicle (AREA)
- Vending Machines For Individual Products (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Lighting Device Outwards From Vehicle And Optical Signal (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14358688A | 1988-01-13 | 1988-01-13 | |
| US143,586 | 1988-01-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1339304C true CA1339304C (fr) | 1997-08-19 |
Family
ID=22504712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000586425A Expired - Lifetime CA1339304C (fr) | 1988-01-13 | 1988-12-20 | Liaison de ligands sur une cible commune |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US5449602A (fr) |
| EP (1) | EP0324616B1 (fr) |
| JP (1) | JP2858771B2 (fr) |
| KR (1) | KR890011998A (fr) |
| AT (1) | ATE120496T1 (fr) |
| AU (1) | AU620065B2 (fr) |
| CA (1) | CA1339304C (fr) |
| DE (1) | DE68921901T2 (fr) |
Families Citing this family (152)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU622426B2 (en) * | 1987-12-11 | 1992-04-09 | Abbott Laboratories | Assay using template-dependent nucleic acid probe reorganization |
| US5449602A (en) * | 1988-01-13 | 1995-09-12 | Amoco Corporation | Template-directed photoligation |
| ATE144556T1 (de) * | 1988-06-24 | 1996-11-15 | Amgen Inc | Verfahren und mittel zum nachweis von nukleinsäuresequenzen |
| US5175273A (en) * | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| US6004826A (en) * | 1988-07-20 | 1999-12-21 | David Segev | Repair-mediated process for amplifying and detecting nucleic acid sequences |
| WO1990001069A1 (fr) * | 1988-07-20 | 1990-02-08 | Segev Diagnostics, Inc. | Procede d'amplification et de detection de sequences d'acide nucleique |
| GR1000347B (el) * | 1988-12-21 | 1992-06-25 | Ortho Diagnostic Systems Inc | Μεθοδος παραγωγης νουκλεοτιδικων ανιχνευτων χρησιμοποιωντας ενα συμπληρωμα γεφυρωσεως. |
| CA2031536A1 (fr) * | 1989-04-05 | 1990-10-06 | Kevin R. Kearney | Reactifs de promotion de l'hybridation |
| US5650302A (en) * | 1990-05-01 | 1997-07-22 | Amgen Inc. | Method for reducing carryover contamination in an amplification procedure |
| US5494810A (en) * | 1990-05-03 | 1996-02-27 | Cornell Research Foundation, Inc. | Thermostable ligase-mediated DNA amplifications system for the detection of genetic disease |
| US5616464A (en) * | 1994-12-27 | 1997-04-01 | Naxcor | Nucleic acid sequence detection employing amplification probes |
| US6495676B1 (en) | 1993-04-13 | 2002-12-17 | Naxcor | Nucleic acid sequence detection employing probes comprising non-nucleosidic coumarin derivatives as polynucleotide-crosslinking agents |
| CA2159356A1 (fr) * | 1993-04-13 | 1994-10-27 | Michael L. Wood | Derives non nucleosidiques de la coumarine , agents de reticulation de polynucleotides |
| US5767259A (en) | 1994-12-27 | 1998-06-16 | Naxcor | Oligonucleotides containing base-free linking groups with photoactivatable side chains |
| US6277570B1 (en) | 1993-04-13 | 2001-08-21 | Naxcor | Nucleic acid sequence detection employing probes comprising non-nucleosidic coumarin derivatives as polynucleotide-crosslinking agents |
| US5846709A (en) * | 1993-06-15 | 1998-12-08 | Imclone Systems Incorporated | Chemical process for amplifying and detecting nucleic acid sequences |
| SE9400522D0 (sv) * | 1994-02-16 | 1994-02-16 | Ulf Landegren | Method and reagent for detecting specific nucleotide sequences |
| USRE38442E1 (en) * | 1994-06-22 | 2004-02-24 | Mount Sinai School Of Medicine | Nucleic acid amplification method hybridization signal amplification method (HSAM) |
| US5942391A (en) | 1994-06-22 | 1999-08-24 | Mount Sinai School Of Medicine | Nucleic acid amplification method: ramification-extension amplification method (RAM) |
| US6593086B2 (en) | 1996-05-20 | 2003-07-15 | Mount Sinai School Of Medicine Of New York University | Nucleic acid amplification methods |
| US5876924A (en) * | 1994-06-22 | 1999-03-02 | Mount Sinai School Of Medicine | Nucleic acid amplification method hybridization signal amplification method (HSAM) |
| EP0717782A1 (fr) * | 1994-06-22 | 1996-06-26 | Mount Sinai School Of Medicine Of The City University Of New York | Amplification dependant de la liaison s'appliquant a la detection d'agents pathogenes infectieux et de genes anormaux |
| US8236493B2 (en) | 1994-10-21 | 2012-08-07 | Affymetrix, Inc. | Methods of enzymatic discrimination enhancement and surface-bound double-stranded DNA |
| US6974666B1 (en) * | 1994-10-21 | 2005-12-13 | Appymetric, Inc. | Methods of enzymatic discrimination enhancement and surface-bound double-stranded DNA |
| SE9403805D0 (sv) * | 1994-11-07 | 1994-11-07 | Ulf Landegren | Method of preparing oligonucleotide probes or primers, vector therefor and use thereof |
| WO1996028438A1 (fr) * | 1995-03-09 | 1996-09-19 | Naxcor | Derives non nucleosidiques de coumarine utilises comme agents de reticulation de polynucleotides |
| WO1996040992A2 (fr) * | 1995-06-07 | 1996-12-19 | Abbott Laboratories | Procede de masquage de sonde servant a limiter le signal d'arriere-plan dans une reaction d'amplification |
| EP0863998A4 (fr) * | 1995-11-03 | 2002-09-25 | Naxcor | Analyse des conformations polymorphiques a double brin |
| AU756301B2 (en) * | 1997-08-20 | 2003-01-09 | Somagenics, Inc. | Antisense and antigene therapeutics with improved binding properties and methods for their use |
| US8337753B2 (en) | 1998-05-01 | 2012-12-25 | Gen-Probe Incorporated | Temperature-controlled incubator having a receptacle mixing mechanism |
| ES2322859T3 (es) | 1998-05-01 | 2009-06-30 | Gen-Probe Incorporated | Analizador de diagnostico automatizado. |
| US6124099A (en) * | 1998-06-22 | 2000-09-26 | The University Of Vermont And State Agricultural College | Method for placing a photo-cross-linking agent at specific internal sites within the sequence of synthetic strands of ribonucleic acids |
| CA2340361A1 (fr) | 1998-08-21 | 2000-03-16 | Peter C. Cheng | Dosages utilisant des acides nucleiques reticulables immobilises |
| US6303799B1 (en) | 1998-11-10 | 2001-10-16 | Naxcor | Polynucleotide crosslinking agents |
| US7014994B1 (en) | 1999-03-19 | 2006-03-21 | Cornell Research Foundation,Inc. | Coupled polymerase chain reaction-restriction-endonuclease digestion-ligase detection reaction process |
| CA2370478A1 (fr) | 1999-03-24 | 2000-09-28 | Serge L. Beaucage | N-acylphosphoramidites et leur utilisation dans la synthese d'oligonucleotides |
| US6372813B1 (en) * | 1999-06-25 | 2002-04-16 | Motorola | Methods and compositions for attachment of biomolecules to solid supports, hydrogels, and hydrogel arrays |
| WO2001016151A1 (fr) * | 1999-08-27 | 2001-03-08 | Japan Science And Technology Corporation | Acide nucleique a photocouplage reversible et phosphoroamidite |
| US7306904B2 (en) * | 2000-02-18 | 2007-12-11 | Olink Ab | Methods and kits for proximity probing |
| JP3753942B2 (ja) * | 2000-03-10 | 2006-03-08 | 独立行政法人科学技術振興機構 | 5−ピリミジン含有核酸、それを用いた可逆的連結方法 |
| US20040067498A1 (en) * | 2000-04-28 | 2004-04-08 | Ahmed Chenna | Detection of nucleic acid sequences by cleavage and separation of tag-containing structures |
| US6562575B1 (en) | 2000-06-26 | 2003-05-13 | Epicentre Technologies Corporation | Analyte-specific assays based on formation of a replicase substrate |
| CA2425663C (fr) | 2000-10-11 | 2009-12-29 | Applera Corporation | Conjugues fluorescents a nucleobase contenant des lieurs anioniques |
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1988
- 1988-01-13 US US07/143,586 patent/US5449602A/en not_active Expired - Lifetime
- 1988-12-20 CA CA000586425A patent/CA1339304C/fr not_active Expired - Lifetime
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1989
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- 1989-01-12 EP EP89300258A patent/EP0324616B1/fr not_active Expired - Lifetime
- 1989-01-12 AT AT89300258T patent/ATE120496T1/de active
- 1989-01-13 AU AU28485/89A patent/AU620065B2/en not_active Ceased
- 1989-01-13 JP JP1007525A patent/JP2858771B2/ja not_active Expired - Lifetime
- 1989-01-13 KR KR1019890000285A patent/KR890011998A/ko not_active Ceased
-
1995
- 1995-05-08 US US08/436,117 patent/US5686243A/en not_active Expired - Lifetime
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1997
- 1997-11-10 US US08/967,011 patent/US6306587B1/en not_active Expired - Fee Related
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|---|---|
| ATE120496T1 (de) | 1995-04-15 |
| EP0324616A2 (fr) | 1989-07-19 |
| US6306587B1 (en) | 2001-10-23 |
| AU2848589A (en) | 1989-07-27 |
| JPH025898A (ja) | 1990-01-10 |
| US5686243A (en) | 1997-11-11 |
| US5449602A (en) | 1995-09-12 |
| DE68921901D1 (de) | 1995-05-04 |
| EP0324616B1 (fr) | 1995-03-29 |
| DE68921901T2 (de) | 1995-08-24 |
| KR890011998A (ko) | 1989-08-23 |
| AU620065B2 (en) | 1992-02-13 |
| JP2858771B2 (ja) | 1999-02-17 |
| EP0324616A3 (en) | 1990-11-14 |
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